Infection with the Hepatitis C Virus (HCV) is generally recognized as a major healthcare problem worldwide. HCV infection can progress to liver fibrosis, which can lead to liver cirrhosis, end-stage liver disease, and HCC (hepatocellular carcinoma), making it the leading cause of liver transplantations. Current standard of care in HCV treatment involves the administration of Pegylated interferon-alpha-2a or Pegylated interferon-alpha-2b in combination with ribavirin during 24 or 48 weeks. Current therapy has its limitations in that only part of the patients is treated successfully, in that it faces significant side effects, is often poorly tolerated, and by its long duration. Hence there is a need for HCV inhibitors that overcome these disadvantages.
Replication of the genome of HCV is mediated by a number of enzymes, amongst which is HCV NS3 serine protease. Various agents have been described that inhibit this enzyme. WO 05/073216 discloses linear and macrocyclic NS3 serine protease inhibitors with a central cyclopentane moiety. WO 2007/014926 discloses a series of macrocyclic NS3 serine protease inhibitors, including salt-forms of these compounds. Amongst these, the compound of formula I with the chemical structure depicted hereinafter, is of particular interest. This compound, with its full chemical name (1R,4R,6S,15R,17R)-cis-N-[17-[2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methyl-quinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl] (cyclopropyl)sulfonamide or (1R,4R,6S,7Z,15R,17R)-N-[17-[2-(4-isopropylthiazol-2-yl)-7-methoxy-8-methylquinolin-4-yloxy]-13-methyl-2,14-dioxo-3,13-diazatricyclo[13.3.0.04,6]octadec-7-ene-4-carbonyl](cyclopropyl)-sulfonamide, is also referred to as “TMC435”. TMC 435 can be prepared by the synthesis procedures described in Example 5 of WO 2007/014926. As used herein, the terms “compound of formula I” and “TMC435” refer to the same chemical entity.
TMC435 not only shows pronounced activity against HCV but also has an attractive pharmacokinetic profile. Clinical investigations show that this compound is well-tolerated in patients and confirm its potential to effectively suppress HCV.

TMC435 is poorly water-soluble and improving its solubility as well as its concomitant bioavailability are desirable targets for drug development. Administering higher doses of poorly soluble drugs could overcome bioavailability problems, but this leads to larger and therefore less practicable dosage forms. Desired are dosage forms that are compact and easy to manufacture.
It is known that bioavailability of poorly soluble active agents can be improved by converting these in amorphous form. Typically, the more crystalline the pharmaceutical agent, the lower is its bioavailability or vice versa, reducing the degree of crystallinity has a positive effect on bioavailability. Amorphous materials generally offer interesting properties such as a higher dissolution rate and solubility than crystalline forms, typically resulting in improved bioavailability. Generating and stabilizing this state typically proves out to be difficult because for many substances the amorphous form is unstable, quickly converting partially or completely to the more stable crystalline form. This conversion is influenced by external factors such as temperature, humidity, traces of crystalline material in the environment, etc. Even amorphous forms that seem stable for long periods of time can convert partially or completely to crystalline forms, sometimes for reasons that are not immediately clear.
The amorphous and crystalline forms not only show differences in bioavailability, but also in their processing properties, such as hygroscopicity, flowability, compaction, and the like. If during the clinical development and manufacture of solid dosage forms the solid form of the drug substance is not stable, the exact amount of the desired form used or studied may vary from one lot to another causing undesired variability not only in therapeutic efficacy but also in manufacturing conditions. Hence, a drug taken into development will almost always be converted into its crystalline form because of its stability in the manufacture and storage of pharmaceutical dosage forms. Very few drugs therefore are available in the amorphous state.
It is an object of the present invention to provide a solid form of the compound of formula I that is stable and has beneficial properties in terms of one or more of the following: its bioavailability, pharmacokinetic properties such as, release rate, area under the curve, and the like; as well as its ability to be formulated, stored and administered as to effectively exert its antiviral properties.
It now has been found that the sodium salt of the compound of formula I can be converted into its amorphous form, which form is surprisingly stable and can advantageously be used as active ingredient in anti-HCV therapy. This form can be converted into pharmaceutical compositions and dosage forms that are compact and easy to manufacture. It further has been found that this form can conveniently be prepared by spray-drying as manufacturing procedure.